title: Mannose receptor-mediated endothelial cell activation contributes to B16 melanoma cell adhesion and metastasis in liver.
abstract: The role of mannose receptors from hepatic sinusoidal endothelium (HSE) in liver colonization by B16 melanoma (B16M) cells was studied. The expression of high mannose-type oligosaccharides on the surface of B16M cells was enhanced by in vitro treatment with 1-deoximannojirimycin (1-DMM). There was a significant (P < 0.01) enhancement of hepatic metastasis when B16M cells were 1-DMM-treated before being intrasplenically injected into C57BL/6J mice. Intraperitoneal administration of 5 mg/kg recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) inhibited the 1-DMM-induced enhancement of metastasis. Expression of high mannose-type oligosaccharides on the surface of 1-DMM-treated B16M cells and their in vitro adhesion to the HSE was significantly correlated (R = 0.82). The addition of either 100 microg/ml mannan or paraformaldehyde (PFA)-fixed 1-DMM-treated B16M cells to cultured HSE for a period of 12 h significantly (P < 0.01) increased the release of IL-1beta from the HSE compared to that liberated by the HSE incubated with either basal medium or PFA-fixed untreated B16M cells. The same HSE treatments also significantly (P < 0.01) increased the degree of adhesion of other B16M cells to HSE, being abrogated by anti-mouse vascular cell adhesion molecule-1 (VCAM-1) antibodies. The conditioned media from HSE cultures, activated by PFA-fixed, 1-DMM-treated B16M cells significantly (P < 0.01) increased B16M cell proliferation when compared to conditioned media from HSE cultures incubated with PFA-fixed, untreated B16M cells. Thus, 1-DMM treatment of B16M cells enhanced the development of hepatic metastasis by IL-1-dependent mechanisms. The mechanism is consistent with in vitro mannose receptor-mediated melanoma cell attachment to the HSE, which subsequently upregulates IL-1beta release, VCAM-1-dependent adherence, and melanoma growth factor(s) release by HSE.
authors.affiliation: Department of Cell Biology and Morphological Sciences, University of the Basque Country, School of Medicine and Dentistry, Vizcaya, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Mendoza
authors.forename: E
authors.initials: E
authors.lastname: Olaso
authors.forename: M J
authors.initials: MJ
authors.lastname: Anasagasti
authors.forename: A M
authors.initials: AM
authors.lastname: Fuentes
authors.forename: F
authors.initials: F
authors.lastname: Vidal-Vanaclocha
mesh_terms: D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D017077:Culture Media, Conditioned / Q000032:analysis; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology; D037181:Lectins, C-Type; D016014:Linear Models; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D007375:Interleukin-1; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D017485:1-Deoxynojirimycin